Proof of Concept of a Binary Blood Assay for Predicting Radiosensitivity

Abstract

Radiation therapy (RT), either alone or in combination with surgery and/or chemotherapy is a keystone of cancers treatment. Early toxicity is common, sometimes leading to discontinuation of treatment. Recent studies stressed the role of the phosphorylated ATM (pATM) protein in RT-toxicity genesis and its ability in predicting individual radiosensitivity (IRS) in fibroblasts. Here we assessed the reliability of the pATM quantification in lymphocytes to predict IRS. A first retrospective study was performed on 150 blood lymphocytes of patients with several cancer types. Patients were divided into 2 groups, according to the grade of experienced toxicity. The global quantity of pATM molecules was assessed by ELISA on lymphocytes to determine the best threshold value. Then, the binary assay was assessed on a validation cohort of 36 patients with head and neck cancers. The quantity of pATM molecules in each sample of the training cohort was found in agreement with the observed Common Terminology Criteria for Adverse Events (CTCAE) grades with an AUC = 0.71 alone and of 0.77 combined to chemotherapy information. In the validation cohort, the same test was conducted with the following performances: sensitivity = 0.84, specificity = 0.54, AUC = 0.70 and 0.72 combined to chemotherapy. This study provides the basis of an easy to perform assay for clinical use.

Human Radiosensitivity and Radiosusceptibility: What Are the Differences?

“…Recently, the delay in the radiation-induced nucleo-shuttling of the ATM protein (RIANS) was shown to be a reliable parameter for predicting radiosensitivity [12,[111][112][113], and to provide a biologically relevant interpretation of the linear-quadratic model, the mathematical basis of the cellular radiation response [114]. In the context of the RIANS model, the following kinetically ordered steps have been observed:…”

Predicting acute severe toxicity for head and neck squamous cell carcinomas by combining dosimetry with a radiosensitivity biomarker: a pilot study

“…This assay gave accurate results, but presented with some issues which could limit its application in the clinical practice, i.e., the need of a skin biopsy, of cell amplification step and of irradiation. To cope with these issues, we first developed an ELISA assay to evaluate pATM in fibroblasts after irradiation and then adapted this assay to the quantification of pATM in blood lymphocytes without irradiation, thus coming to the RADIODTECT© [32]. This pilot study also acts as a feasibility study on use of RADIODTECT© in a clinical setting.…”

“…The training cohort described elsewhere [32] was used to determine the threshold i.e. 57.8 ng/mL for grade≥2 toxicity [32].…”

“…The training cohort described elsewhere [32] was used to determine the threshold i.e. 57.8 ng/mL for grade≥2 toxicity [32]. However, this cohort with different types of cancer included only 23 patients with grade≥3 toxicity [32].…”

“…57.8 ng/mL for grade≥2 toxicity [32]. However, this cohort with different types of cancer included only 23 patients with grade≥3 toxicity [32]. Because grade≥3 toxicity are more frequent in HNSCC patients, we used another cohort including 53 HNSCC patients to verify the threshold for grade≥2 toxicity obtained previously [32] and determine the threshold for grade≥3 toxicity in HNSCC.…”